Study to Evaluate the Effect of Renal Impairment and Dialysis Treatment on the Pharmacokinetics of a Single 3 mg Cytisinicline Dose

NCT05631938 | Completed Phase 1 FDA Drug

• 1 other identifier: ACH-CYT-05
• Study Type: interventional
• Target: 44
• Locations: 2 countries
• Sites: 6

Brief Summary

The primary objectives of this study are:

1. 1.To obtain information on the pharmacokinetics of cytisinicline following a single oral dose in subjects with varying degrees of renal impairment relative to matched controls with normal renal function.
2. 2.To investigate the extent of cytisinicline removal by hemodialysis.

Conditions

Renal Impairment

Keywords

Dialysis

Outcome Measures

Primary Outcomes (19)

• Plasma Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax)

  pre-dose; 00:20, 00:40, 01:00, 01:20, 01:40, 02:00, 02:30, 03:00, 04:30, 06:00, 08:00, 12:00; 24:00, 36:00 and 48:00 hours:minutes post-dose

• Plasma PK Parameter: Time of Occurrence of Cmax (Tmax)

  pre-dose; 00:20, 00:40, 01:00, 01:20, 01:40, 02:00, 02:30, 03:00, 04:30, 06:00, 08:00, 12:00; 24:00, 36:00 and 48:00 hours:minutes post-dose

• Plasma PK Parameter: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time of Dosing (t=0h) to the Time of the Last Measurable Concentration (AUC0-t)

  pre-dose; 00:20, 00:40, 01:00, 01:20, 01:40, 02:00, 02:30, 03:00, 04:30, 06:00, 08:00, 12:00; 24:00, 36:00 and 48:00 hours:minutes post-dose

• Plasma PK Parameter: Total AUC Extrapolated to Infinity (AUC0-∞)

  pre-dose; 00:20, 00:40, 01:00, 01:20, 01:40, 02:00, 02:30, 03:00, 04:30, 06:00, 08:00, 12:00; 24:00, 36:00 and 48:00 hours:minutes post-dose

• Plasma PK Parameter: Apparent Terminal Elimination Rate Constant (λz)

  pre-dose; 00:20, 00:40, 01:00, 01:20, 01:40, 02:00, 02:30, 03:00, 04:30, 06:00, 08:00, 12:00; 24:00, 36:00 and 48:00 hours:minutes post-dose

• Plasma PK Parameter: Apparent Terminal Elimination Half-Life (t1/2)

  pre-dose; 00:20, 00:40, 01:00, 01:20, 01:40, 02:00, 02:30, 03:00, 04:30, 06:00, 08:00, 12:00; 24:00, 36:00 and 48:00 hours:minutes post-dose

• Plasma PK Parameter: Fraction Unbound (fu)

  pre-dose; 00:20, 00:40, 01:00, 01:20, 01:40, 02:00, 02:30, 03:00, 04:30, 06:00, 08:00, 12:00; 24:00, 36:00 and 48:00 hours:minutes post-dose

• Plasma PK Parameter: Apparent Clearance (CL/F)

  pre-dose; 00:20, 00:40, 01:00, 01:20, 01:40, 02:00, 02:30, 03:00, 04:30, 06:00, 08:00, 12:00; 24:00, 36:00 and 48:00 hours:minutes post-dose

• Plasma PK Parameter: Apparent Volume of Distribution (V/F)

  pre-dose; 00:20, 00:40, 01:00, 01:20, 01:40, 02:00, 02:30, 03:00, 04:30, 06:00, 08:00, 12:00; 24:00, 36:00 and 48:00 hours:minutes post-dose

• Urine PK Parameter: Amount of Drug Excreted in Urine (Ae)

  pre-dose, 00:00-04:00 (groups 1-4), 00:00-06:00 (group 5), 04:00-08:00 (groups 1-4), 06:00-08:00 (group 5), 08:00-12:00, 12:00-24:00, 24:00-36:00 and 36:00-48:00 hours:minutes post-dose

• Urine PK Parameter: Fraction of Unchanged Drug Excreted in Urine (fe)

  pre-dose, 00:00-04:00 (groups 1-4), 00:00-06:00 (group 5), 04:00-08:00 (groups 1-4), 06:00-08:00 (group 5), 08:00-12:00, 12:00-24:00, 24:00-36:00 and 36:00-48:00 hours:minutes post-dose

• Urine PK Parameter: Area Under the Urine Excretion Rate Curve From Time Zero to Last Measurable Observed Excretion Rate (AURC)

  pre-dose, 00:00-04:00 (groups 1-4), 00:00-06:00 (group 5), 04:00-08:00 (groups 1-4), 06:00-08:00 (group 5), 08:00-12:00, 12:00-24:00, 24:00-36:00 and 36:00-48:00 hours:minutes post-dose

• Urine PK Parameter: Renal Clearance (CLR)

  pre-dose, 00:00-04:00 (groups 1-4), 00:00-06:00 (group 5), 04:00-08:00 (groups 1-4), 06:00-08:00 (group 5), 08:00-12:00, 12:00-24:00, 24:00-36:00 and 36:00-48:00 hours:minutes post-dose

• Urine PK Parameter: Apparent Nonrenal Clearance (CLNR/F)

  pre-dose, 00:00-04:00 (groups 1-4), 00:00-06:00 (group 5), 04:00-08:00 (groups 1-4), 06:00-08:00 (group 5), 08:00-12:00, 12:00-24:00, 24:00-36:00 and 36:00-48:00 hours:minutes post-dose

• PK Parameter in Dialysate, Group 5 (ESRD on-dialysis): Amount of Drug Recovered From Each Dialysate Collection (AD)

  Day 1 pre-dialysis, post-dialysis (before the hemodialysis is stopped), and for 1 minute every hour during hemodialysis

• PK Parameter in Dialysate, Group 5 (ESRD on-dialysis): Cumulative Amount of Drug Recovered From the Dialysate (AD, total)

  Day 1 pre-dialysis, post-dialysis (before the hemodialysis is stopped), and for 1 minute every hour during hemodialysis

• PK Parameter in Dialysate, Group 5 (ESRD on-dialysis): Partial Area Under the Curve Estimated From Predialyzer Samples Collected From Start of Dialysis (t0) to End of Dialysis (t1) (AUCt0-t1)

  Day 1 pre-dialysis, post-dialysis (before the hemodialysis is stopped), and for 1 minute every hour during hemodialysis

• PK Parameter in Dialysate, Group 5 (ESRD on-dialysis): Dialysis Clearance (CLD)

  Day 1 pre-dialysis, post-dialysis (before the hemodialysis is stopped), and for 1 minute every hour during hemodialysis

• PK Parameter in Dialysate, Group 5 (ESRD on-dialysis): Fraction of the Administered Dose That is Recovered in the Dialysate (Frem)

  Day 1 pre-dialysis, post-dialysis (before the hemodialysis is stopped), and for 1 minute every hour during hemodialysis

Secondary Outcomes (9)

• Number of Participants With Clinically Significant Changes from Baseline in Body Weight

  Baseline (pre-dose), 48 hours post-dose

• Number of Participants With Clinically Significant Changes from Baseline in Systolic and Diastolic Blood Pressure

  Baseline (pre-dose), 2, 6, 24, 36 and 48 hours post-dose

• Number of Participants With Clinically Significant Changes from Baseline in Pulse Rate

  Baseline (pre-dose), 2, 6, 24, 36 and 48 hours post-dose

• Number of Participants With Clinically Significant Changes from Baseline in Body Temperature

  Baseline (pre-dose), 2, 6, 24, 36 and 48 hours post-dose

• Number of Participants With Clinically Significant Changes from Baseline in Hematology Values

  Baseline (pre-dose), 48 hours post-dose

Study Arms (5)

Group 1: Normal Renal Function

EXPERIMENTAL

Participants with normal renal function receive a 3 mg single dose of cytisinicline.

Drug: cytisinicline

Group 2: Mild Renal Impairment

EXPERIMENTAL

Participants with mild renal impairment receive a 3 mg single dose of cytisinicline.

Drug: cytisinicline

Group 3: Moderate Renal Impairment

EXPERIMENTAL

Participants with moderate renal impairment receive a 3 mg single dose of cytisinicline.

Drug: cytisinicline

Group 4: Severe Renal Impairment

EXPERIMENTAL

Participants with severe renal impairment receive a 3 mg single dose of cytisinicline.

Drug: cytisinicline

Group 5: ESRD Participants Undergoing Dialysis

EXPERIMENTAL

Participants with ESRD undergoing dialysis receive a 3 mg single dose of cytisinicline on 2 occasions: after and prior to a dialysis session.

Drug: cytisinicline

Interventions

cytisinicline DRUG

film-coated oral tablets containing 3 mg cytisinicline

Also known as: cytisine

Group 1: Normal Renal Function; Group 2: Mild Renal Impairment; Group 3: Moderate Renal Impairment; Group 4: Severe Renal Impairment; Group 5: ESRD Participants Undergoing Dialysis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Free written informed consent prior to any procedure required by the study.
• Ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the requirements of the study.
• Willingness to accept and comply with all study procedures and restrictions.
• Male or female subject between 18 and 75 years, inclusive, at Screening.
• Body mass index (BMI) of 18.0 to 35.0 kg/m\^2, inclusive, at Screening.
• A female subject is eligible if she meets one of the following criteria:
• is of non-childbearing potential (underwent a permanent sterilization method \[e.g., hysterectomy, bilateral salpingectomy and bilateral oophorectomy\], is clinically diagnosed infertile, or is in a post-menopausal state); or
• is of childbearing potential and agrees to use an accepted contraceptive method from at least 28 days prior to dose administration (prior to first dose administration for Group 5) until at least 1 month after the end of study (EOS).
• Negative test results for anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV-1Ab and anti-HIV-2Ab), hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibodies (anti-HCVAb).
• Stable concomitant medications for at least 7 days prior to dose administration (first dose administration for Group 5) and up to the EOS.
• eGFR at Screening, determined by the Cockcroft-Gault equation, within:
• mL/min for Group 2 (mild renal impairment subjects).
• mL/min for Group 3 (moderate renal impairment subjects).
• mL/min for Group 4 (severe renal impairment subjects).
• \<15 mL/min for Group 5 (ESRD subjects)

You may not qualify if:

• Known hypersensitivity/allergy reaction to cytisinicline substance or any of the excipients.
• History of renal, heart, and/or liver transplant.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere in a relevant manner with the absorption, distribution, metabolism, or excretion of the study treatment except for renal disease.
• Symptoms of an acute clinically relevant infection in the 4-week period preceding Screening (e.g., bacterial, viral, or fungal infection).
• History or clinical evidence of alcohol use disorder or substance use disorder according to Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) classification, within the 3-year period prior to Screening.
• Clinically relevant abnormalities on a 12-lead electrocardiogram (ECG), recorded after 5 min in the supine position at Screening.
• Currently using any creatine supplement.
• Nicotine consumption (e.g., smoking, nicotine patch, nicotine chewing gum, or electronic cigarettes) from 48 hours prior to Admission.
• Excessive caffeine consumption, defined as ≥800 mg per day at Screening.
• Positive result in drugs-of-abuse or ethanol tests at Screening or Admission. NOTE: Subjects receiving stable treatment of methadone and benzodiazepines will be allowed to be enrolled in the study even if the urine drug screen test is positive.
• Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
• Participation in any clinical trial within the previous 2 months.
• Loss of 250 mL or more blood within 3 months prior to screening.
• If female, positive pregnancy test in serum at Screening or positive pregnancy test in urine at Admission.
• If female, she is breast-feeding.

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (6)

Hospital de Braga, Centro Clínico Académico Braga, Associação

Braga, Braga District, 4710-243, Portugal

Location

BlueClinical Phase I

Porto, Porto District, 4250-449, Portugal

Location

Early Phase Clinical Trials Unit | CHVNG/E + BlueClinical

Vila Nova de Gaia, Porto District, 4434-502, Portugal

Location

Hospital Universitario de La Princessa

Madrid, Madrid, 28006, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

cytisine

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Serafim Guimarães, MD, PhD

  Blueclinical, Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: November 30, 2022
• Study Start: January 10, 2023
• Primary Completion: September 4, 2023
• Study Completion: September 4, 2023
• Last Updated: July 11, 2025

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); PT (3)